Positron Emission Tomography (PET)

PET is a nuclear medicine technique using a camera, which captures images of the human body's function. Compounds normally existing in the body, like simple sugars, are labeled with radioactive tracers, and are injected into the body intravenously. The tracer emits signals which are recorded by the scanner as the tracer travels through the body and/or collects in targeted organs. A computer reassembles the signals into actual images, which then show biological maps of normal organ function and failure of organ systems in disease.

The basic steps of PET imaging include radioisotope production, radiopharmaceutical chemistry, tomographic acquisition, and image re-construction.

A. An isotope of fluorine (fluorine-18) is made in the cyclotron and chemically inserted into deoxyglucose.

B. 18-fluorodeoxyglucose is injected into the subject who is then imaged in the PET scanner.

C. An image, showing localization of the fluorine isotope, is formed.

The GE PETtrace cyclotron generates fast moving subatomic particles which, on collision with the appropriate target substance, generate a useful radioactive isotope, such as 18-Fluorine, a positron emitter. The cyclotron is housed in the basement of the Huntsman Cancer Institute and is managed by Mr. Paul Christian.

The GE PETrace Cyclotron

The positron-emitting isotope may be used alone or is chemically incorporated into a molecule that, on injection into the subject, will tend to accumulate in a tissue of interest. 18-Fluorine, for example, is often incorporated into a form of glucose to form 18-F-fluorodeoxyglucose or FDG. FDG, or rather its metabolites, accumulate in tissues with high metabolic activity, such as a tumor.

A PET scanner does not image human anatomy. It can only detect, and represent as an image, positron-emitting isotopes. On decay of the isotope, the emitted positron will travel only a few thousandths of a millimeter (1 to 2 microns), whereupon it annihilates and releases two photons moving in exactly opposite directions. This has two consequences:

Firstly, it makes possible location of the point of positron annihilation. The PET scanner detects and records photons that arrive at the scanner's detectors simultaneously and moving in opposite directions. Photons that originate from other forms of radioactive decay may thus be eliminated from the record. In addition, by computing the line between the two points at which the photons were incident on the scanner, the location of the emitting isotope is known in 2-dimensions. If enough such photons are detected, the location may then be calculated in 3-dimensions.

Secondly, travel of the positron away from the location of the isotope before decaying to emit the two photons defines the precision with which the isotope itself may be located. The resolution of a PET scanner is therefore approximately 2 microns.

Some examples of images made with a PET scanner

A full-body PET scan of a patient. Note that the "anatomy' of the patient may be discerned, but the image is based entirely on emissions from the PET tracer (18-FDG).

To get a clearer idea of the location of "hot-spots" (sites of isotope accumulation), a CT scan showing actual anatomical features is performed on the patient at approximately the same time:

and the images are overlayed:

+ =

To facilitate this process the two types of imaging device are built into a single framework, the PET/CT scanner. PET/CT imaging is available at the Huntsman Cancer Institute.

Note that these images were made with a tracer that accumulates at sites of increased metabolic activity. The images therefore show not just a tissue's location, but tell us something of what the tissue is doing; in this case, "burning" glucose. This principal may be extended. Using the appropriate tracer, a PET image can provide information on an enormous variety of tissue functions. For example, gene expression.

Imaging Gene Expression
PET can image gene expression in vivo using a variety of approaches. One such example is enzyme-mediated trapping with the HSV1-tk reporter gene. The HSV1-tk enzyme phosphorylates the radiolabeled reporter probe, in this case [ 18 F]-FGCV, thereby trapping it in cells where the reporter gene is expressed. Endogenous gene expression can also be imaged by matching the promoter of the endogenous gene of interest to the HSV1-tk reporter gene. Other approaches include receptor-ligand mediated trapping and RASON binding to mRNA. [Diagram courtesy of Gary T. Smith, M.D.]

PET Imaging in Research
The University of Utah now has access to a micro PET scanner, designed to image smaller subjects, such as experimental animals. The advantages to both investigator and subject are enormous. Metabolic processes can be followed in real-time in the live animal with no more discomfort to the animal than would be experienced by a patient. Assays can be repeated in the same animal, vastly improving the validity of the observations and reducing the number of animals required.

Example microPET images: 18 F- mouse bone scan (left), rat striatal dopamine system (upper right), and healthy rat heart imaged with FDG (lower right). Images courtesy of Crump Institute for Biological Imaging, UCLA